Authors: Wang J-Y et al.
Anesthesiology. December 2025.
Summary
This retrospective multicenter cohort study examined whether critical closing pressure (Pcc) and tissue perfusion pressure (TPP) provide prognostic information beyond mean arterial pressure (MAP) for risk stratification in patients with sepsis. While MAP is the cornerstone hemodynamic target in sepsis management, it does not directly account for microvascular flow cessation or vascular tone, which may contribute to impaired tissue perfusion despite “adequate” pressures.
The investigators analyzed data from 6,769 adult patients with sepsis across 18 hospitals using two independent datasets. Pcc was estimated using linear regression of hourly MAP against the product of heart rate and pulse pressure, reflecting the arterial pressure at which blood flow ceases. TPP was calculated as the difference between MAP and Pcc, representing the effective driving pressure for tissue perfusion. Patients were categorized into four groups based on early (first 24 hours) Pcc and TPP values.
Outcomes demonstrated clear stratification by Pcc–TPP phenotype. ICU mortality was highest in patients with both low TPP and low Pcc and lowest in those with high TPP and high Pcc. Similar gradients were observed for short-term mortality and development of acute kidney injury. Importantly, after adjustment for MAP, a U-shaped association emerged: higher Pcc combined with reduced TPP was independently associated with increased mortality and AKI risk. These findings were externally validated in the MIMIC-IV cohort, strengthening their robustness.
The study highlights that two patients with the same MAP may have markedly different tissue perfusion depending on vascular tone and critical closing pressure. By capturing these physiologic nuances, Pcc and TPP appear to complement MAP and may help identify patients at higher risk for organ dysfunction and death who might otherwise be missed using MAP-based targets alone.
Key Points
Critical closing pressure reflects the arterial pressure at which microvascular flow ceases and influences effective perfusion.
Tissue perfusion pressure (MAP minus Pcc) better represents the driving force for blood flow than MAP alone.
Low TPP combined with unfavorable Pcc was associated with higher mortality and acute kidney injury in sepsis.
The relationship between Pcc, TPP, and outcomes persisted after adjustment for MAP.
Incorporating Pcc and TPP into hemodynamic assessment may improve risk stratification and guide individualized blood pressure management in sepsis.
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